Finasteride, also known as N-(5α,17β)-N-(1,1-dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide, is a 5α-reductase inhibitor, functions in many androgen-sensitive tissues by converting the major circulating androgenic hormone, testosterone, into the intracellular androgenic metabolite dihydrotestosterone (DHT). Finasteride is used in the treatment of hyperandrogenic conditions, such as acne vulgaris, seborrhea, female hirsutism and benign prostate hypertrophy.
Finasteride was first disclosed in U.S. Pat. No. 4,760,071, which describes a process wherein the carboxylic group at the 17β-position of 3-oxo-4-aza-5a-androstane-17β-carboxylic acid of formula (II) is converted into a pyridylthioester group of formula (III) using 2,2′-pyridyldisulfide. The compound of formula (III) is reacted with tert-butylamine to obtain 17β-tert-butylamide of formula (IV), followed by introducing a double bond between the first and the second carbon atoms using benzeneselenic anhydride in boiling chlorobenzene to obtain finasteride of formula (I). However, this process suffers from a high production cost due to the usage of expensive reagents such as 2,2′-pyridyldisulfide and bezeneselenic anhydride, and a poor purity, due to the formation of undesired by-products. Further, it is difficult to improve the purity of the obtained finasteride even after purification steps such as column chromatography and recrystallization.

U.S. Pat. No. 5,084,574 discloses a process for preparing finasteride, which comprises silylating the 3-oxo group in the above compound of formula (II) using bistrimethylsilyltrifluoroacetamide (BSTFA), followed by introducing a double bond using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an oxidizing agent. However, the isolation of finasteride from the reaction mixture by this process is very difficult, and one obtains only impure finasteride. Further purification of finasteride at this stage is much more difficult, therefore, it is not suitable for mass production.
U.S. Pat. No. 5,091,534 describes a process for preparing finasteride, which comprises silylating the compound of the formula (II) in the presence of a base and introducing a halogen such as iodine and bromine into the 2-position of the compound, followed by introducing a double bond between the first and the second carbon atoms using a strong base such as potassium tert-butoxide, 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and 1,5-diazabicyclo [4.3.0] non-5-ene (DBN).
However, this process also suffers from product of a poor quality, since the reactants and products tend to decompose due to the high pH of the reaction solution owing to the strong base.
U.S. Pat. No. 5,021,575 describes a process wherein azasteroid has been first treated with oxalyl chloride to protect amide nitrogen and oxygen and then subjected to bromination to prepare 2-bromo derivative of azasteroid. Thereafter 2-bromo derivative is deprotected first, followed by dehydrohalogenation to create Δ1,2-double bond. However, this process involves complicated reactions leading to unwanted by-products.
U.S. Pat. No. 6,762,302 describes the bioconversion process to effect dehydrogenation during preparation of finasteride. However, the best reported yield was 80% conversion and furthermore this patent does not teach, how to remove the unreacted dihydrofinasteride, which is difficult to remove by crystallization.
As discussed, the above described methods for preparing finasteride are disadvantageous in that they employ expensive and toxic reagents, require extreme reaction conditions or comprise complicated multiple steps, thereby rendering them unsuitable for mass production. Accordingly, there has been a need to develop a simple and industrially viable process by using novel intermediates of formula V and formula VI (protected finasteride), which can be easily purified to obtain a highly pure finasteride, in higher yield.